What is neural stemness? Why is it important? What are the molecular signatures of neural stemness? What are the regulatory networks that control neural stemness? transcriptome epigenome proteome Neural stemness

Bottom-up – single gene (REST) Map genome binding sites Map loci that are transcriptionally and/or epigenetically regulated Knock gene out in cells and mice & look at effect on function But – which aspects of transcriptional and epigenetic regulation are critical to this function? Looking for networks Top-down – networks Isolating defined regulatory modules Inferring regulatory modules

Challenges Bottom-up: what does a network look like from a single genes point of view Top-down: what does a network look like from a global point of view Integrate all the omes to enable a network to include knowledge of the transcriptome, epigenome and proteome Find a way to conceptualise, model and test such networks Prove the value by manipulating a neural stem cell at will to any desired outcome